1. Technical Field
This document relates to methods and materials involved in detecting genetic mutations involved in loss of hair pigmentation and increased cancer susceptibility (e.g., increase susceptibility to form melanomas). This document also relates to methods and materials involved in treating cancer (e.g., melanoma).
2. Background Information
Grey horses are born colored but gradually loose hair pigmentation and eventually, by the age of 6-8 years, become shining white. The dominant Grey allele, manifested as a splendid white horse, has had a high impact on human culture and has left numerous marks in art and literature (e.g., Pegasus and the Unicorn) from Asia and Europe. It has most certainly been selected by humans due to the prestige of riding a white horse with its mystic charisma. Numerous kings, emperors, and other prominent people have been portrayed on a white horse. The mutation appears to have arisen more than 2,000 years ago since white horses are mentioned in ancient Greek literature as well as in the Bible; the Grey locus is by far the most common cause of white coat color in horses (Sponenberg, “Equine Coat Color Genetics,” (Blackwell, Ames, Iowa, 2003)).
Grey causes a gradual loss of hair pigmentation whereas dark skin pigmentation is maintained. Furthermore, Grey horses can exhibit vitiligo and a very high incidence of dermal melanomas. It has been estimated that 70-80% of Grey horses older than 15 years of age possess melanomas (Sutton and Coleman, 1-34, R1RDC, Barton, Australia (1997) and Fleury et al., Pigment Cell Res., 13:47-51 (2000)) and that the Grey mutation reduces longevity (Comfort, Nature, 182:1531-1532 (1958)).
The melanomas occur primarily as jet black firm nodules in the dermis of glabrous skin (e.g., under the tail root, in the anal, perianal, and genital regions, perineum, lips, and eyelids; Seltenhammer et al., Pigment Cell Res., 17:674-681 (2004)). Initially, these primary multiple melanomas are benign but some develop metastases in several internal organs.